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1. ALMOOSA, KHALID FAEQ. QUALITY OF DISCUSSIONS ON RESUSCITATION BETWEEN ICU PHYSICIANS AND CRITICALLY ILL PATIENTS' SURROGATE DECISION MAKERS.

Degree: MS, Medicine : Environmental Health, 2007, University of Cincinnati

► Background. Critically ill patients are often unable to participate in discussions about… (more)

▼ Background. Critically ill patients are often unable to participate in discussions about resuscitation in the event of a cardiopulmonary arrest, leaving their surrogates to make these decisions on their behalf. The ability of surrogates to make these decisions, however, depends on the quality of communication with physicians regarding the resuscitation process and its outcomes. There are few data on the frequency and quality of these discussions about resuscitation and how they are perceived by the surrogates. Methods. Surrogates of critically ill patients who were not able to make decisions about resuscitation at the University Hospital, Cincinnati, and the Cincinnati Veterans Affairs Medical Center were offered the opportunity to participate in a questionnaire designed to elicit information about the quality of communications with the physicians. Enrolled subjects were interviewed using a structured questionnaire in person or over the phone. Additional data regarding the patients’ ICU course and outcomes were collected from their medical records. Results. Of 38 surrogates who participated in the survey, 21 (55%) recalled participating in a discussion on resuscitation with the ICU physicians. Surrogates were usually spouses (33%) or children (41%) of the patients, 52 + 12 years of age, and mostly (89%) high school educated. Discussions lasted an average of 18 + 15 minutes, and were often multiple, with other family and friends also present. Most discussions included the topics of chest compressions, electrical cardioversion, and endotracheal intubation, and these topics were well understood by most surrogates. Surrogates were generally (80%) satisfied with these discussions, and most believed they facilitated making a decision about resuscitation. Conclusion. A large proportion of hospitalized patients’ surrogates had not participated in a discussion on resuscitation within the first several days of the patient’s stay in the ICU. For those who had participated, most understood the contents of the discussions and were generally satisfied with them. Advisors/Committee Members: Kralovic, Dr. Stephen.

Keywords: Resuscitation; Discussion; Critical Illness

2. Anderson, Lisa N. Natural History of Allergic Sensitization in High-Risk Infants.

Degree: MS, Medicine : Environmental Health, 2007, University of Cincinnati

► Objectives: Characterize the natural history of allergic sensitization and compare three definitions… (more)

Keywords: Infants; Allergy; Sensitization; Allergy Testing; Skin Prick Test; Prevalence

3. BARNES-ELLERBE, SONJA JEANETTE. MECHANISMS OF AROMATIC HYDROCARBON RECEPTOR-MEDIATED DISRUPTION OF ANDROGEN RECEPTOR FUNCTION.

Degree: PhD, Medicine : Environmental Health, 2004, University of Cincinnati

► The mechanism by which TCDD, through an aromatic hydrocarbon receptor (AHR) mediated… (more)

▼ The mechanism by which TCDD, through an aromatic hydrocarbon receptor (AHR) mediated pathway, blocks androgen receptor (AR) function has yet to be fully characterized. Human-derived, androgen-dependent Lymph Node Cancer of the Prostate (LNCaP) cells were used to study the effects of TCDD on androgen-regulated cell proliferation and gene transcription. TCDD blocks androgen-induced cell proliferation measured by trypan blue exclusion and 5’bromo-deoxyuridine (BrdU) uptake in LNCaP cells. TCDD treatment alone or in co-treatment with androgen did not decrease cell viability. Western blot analyses reveal that decreases in androgen-induced cell proliferation by TCDD correlates well with increases in hypophosphorylated retinoblastoma protein (RB) and with concomitant decreases in cyclin D1 protein levels, which are key regulatory proteins governing G1-S phase progression. The expression of cyclin-dependent kinase inhibitor p21WAF1/CIP1 was enhanced by TCDD treatment. In addition, reporter gene assays reveal AHR-responsive elements present in the promoter and first intron of the p21WAF1/CIP1 gene that respond to TCDD-mediated AHR activation independently of p53 expression in human-derived prostate and breast cancer cell lines. This is indicative that the AHR may play a role in cell cycle progression by regulating the expressions and/or activities of cyclin/cdk complexes and ckis that regulate RB phosphorylation. Transient transfections studies also show activation of AHR can block the androgen-dependent activity of human and rat derived androgen-responsive gene promoters in LNCaP as well as in African green monkey CV-1 cells. Over-expression of ARNT showed no effect. AHR blocked the activity of both wild-type and LNCaP-derived mutant AR expressed in CV-1 cells. TCDD did not decrease the levels of nuclear AR or compete for binding to AR. Interestingly, AHR mediated transcription of an XRE-driven luciferase reporter construct was enhanced by androgen treatment in LNCaP cells and by AR co-transfection with AHR in CV-1 cells, indicating a possible cross-talk between the two pathways at the transcriptional level. In conclusion, these data point to at least three mechanisms whereby TCDD blocks AR function in LNCaP cells: (1) by blocking androgen-induced cell proliferation in LNCaP cells through modulating the activity of cell cycle regulatory proteins, (2) through interfering with AR-mediated transcriptional activity, and/or (3) through cross-talk of AR- and AHR-mediated signal transduction pathways, possibly involving competition for coregulators, direct protein interaction, or by blocking AR posttransciptional modification. Advisors/Committee Members: Puga, Dr. Alvaro.

Subjects: Biology, Molecular

4. Barth, Edwin F. III. Evaluation of Bioaerosol Components, Generation Factors, and Airborne Transport Associated with Lime Treatment of Lead-Contaminated Sediment for Beneficial Use Purposes.

Degree: PhD, Medicine : Environmental Health, 2006, University of Cincinnati

► Existing technical guidance from public health and occupational safety agencies typically focus… (more)

▼ Existing technical guidance from public health and occupational safety agencies typically focus on potential chemical exposures more so than potential biological agent exposure during contaminated sediment management activities. A physical model of a contaminated sediment treatment and airborne transport process, and an experimental protocol were developed to evaluate the effectiveness of lime treatment to reduce the physiological and environmental availability of lead, identify specific components (bacteria, fungi, cell structural components, and particulates) of a bioaerosol that may be generated from such a treatment process, and the key reaction variables (amount of lime addition, rate of lime addition, mixing energy supplied) that effect the amount of bioaerosol components that may be generated. Lime treatment of a sediment contaminated with heavy metals, petroleum-based organics, and microorganisms increased the sediment pH and solids content of the sediment, but increased the bioaccessibility of lead in the bloodstream as measured by an in-vitro laboratory method. Lime treatment reduced the amount of endotoxin in the sediment, but the effects of lime treatment on β-d glucan could not be determined. Lime treatment reduced the number of water-extractable bacteria in the sediment from approximately 106 CFU/ml to less than 103 CFU/ml and reduced the number of water-extractable fungi from approximately 106 CFU/ml to less than 103 CFU/ml within 14 days. The temperature of the sediment was linearly related to the amount of lime added. Bacteria were aerosolized during the treatment trials, suggesting that public health and occupational safety agencies should consider such exposure. There was no evidence of aerosolization of fungi above the detection limit during the treatment trials, most likely due to either their larger particle size that could not be collected by the impingers, or their particular growth stage. Non-biological particulates, endotoxin and β-d glucan were not detected in air samples during the treatment trials. The amount of lime added to the reaction and the mixing energy supplied to the reaction significantly effected the aerosolization ratio of bacteria (amount of aerosolized bacteria divided by amount of bacteria in untreated sediment) from the reaction beaker. For the majority of the treatment trials, an increase in the mixing energy input increased the aerosolization ratio. For the majority of the treatment trials, an increase in the amount of lime added decreased the aerosolization ratio. The rate of lime addition did not significantly effect the aerosolization ratio of bacteria Advisors/Committee Members: Clark, Dr. Scott C.

Keywords: bioaerosol; sediment; lead; lime

5. Djawe, Kpandja. The changes of antibody levels to MsgC variants over time in HIV-infected men.

Degree: MS, Medicine : Environmental Health, 2008, University of Cincinnati

► The Major Surface Glycoprotein (Msg) is a crucial protein complex in Pneumocystis… (more)

Subjects: Biomedical research; Immunology

6. Eninger, Robert M. Performance Aspects of Filtering Facepiece Respirators Against Ultrafine Inert and Biological Particles.

Degree: PhD, Medicine : Environmental Health, 2008, University of Cincinnati

► Aspects of filter testing and performance of filtering-facepiece respirators (FFRs) were investigated… (more)

▼ Aspects of filter testing and performance of filtering-facepiece respirators (FFRs) were investigated with focus on particles in the ultrafine size range. Three specific aims were pursued in four related studies. In the first study, the contribution to measured concentration made by the ultrafine fraction of the NIOSH respirator filtration test aerosols was theoretically modeled and tested. The most-penetrating particle size (MPPS) for N-type filters was observed in the ultrafine size range under laboratory conditions; also, ultrafine particles did not materially contribute to NIOSH’s respirator filter test protocol. The second study compared filter penetration and MPPS for N99 and N95 FFR’s when challenged with ultrafine inert (NaCl) and biological aerosols (3 test viruses). The MPPS was observed in the ultrafine size for all respirators and test aerosols under conditions similar to the NIOSH filter test protocol. Inert particles penetrated filters similarly to virus particles, with several exceptions which were explainable and attributed to the physical and electrical properties of virus particles. The third study developed and evaluated a method to compare physical and biological (viable count) filtration efficiency of two traditional respirators and one newly designed FFR with an iodinated treatment. The physical and viable virus penetrations were not found to differ for all three respirators; no killing effect was observed in virus particles which penetrated the filter medium. An additional study assessed the appropriateness of nebulization to aerosolize virions for use in filter testing. An experiment was conducted to compare bioaerosol filter testing using nebulization to that of charge-reduced electrospray. The nebulizer protocol was observed to be reasonably robust and it was concluded that nebulization is an appropriate method to use for aerosolizing virions for filter testing with appropriate protocols. Overall, this dissertation contributed several key observations: (1) the definition of the "most conservative" test conditions for respirator filter testing was refined; (2) the understanding of factors which contribute to filtration differences of ultrafine biological and inert particles was increased; (3) a novel method was developed to differentiate physical and viable bioaerosol filter penetrations, and (4) the first practical comparison of nebulization and electrospray for aerosolizing virions was performed. Advisors/Committee Members: Grinshpun, Sergey.

Subjects: Environmental science; Occupational safety

Keywords: ultrafine; filtration; inert; biological; electrospray

7. Hammer, Matthew Justin. Ergonomic Comparison of Keyboard and Touch Screen Data Entry While Standing and Sitting.

Degree: MS, Medicine : Environmental Health, 2007, University of Cincinnati

► Data entry is a common practice in many facilities throughout the world.… (more)

Keywords: ergonomics; biomechanics; kinematics; data entry; touch screen; keyboard; sit stand table; call center

8. Iossifova, Yulia Yulianova. (1-3)-β-D-glucans in indoor environments – laboratory analysis and wheeze in infants.

Degree: PhD, Medicine : Environmental Health, 2006, University of Cincinnati

► Indoor exposure to fungi has been associated with respiratory symptoms, often attributed… (more)

▼ Indoor exposure to fungi has been associated with respiratory symptoms, often attributed to their major cell wall component, (1-3)-β-D-glucan. Currently there are two methods available for the analysis of (1-3)-β-D-glucan: the Limulus Amebocyte Lysate assay (LAL) and the inhibition Enzyme Immunoassay (EIA). (1-3)-β-D-glucan is a fungal cell wall component, suspected to cause respiratory and general symptoms in adults. However, very little is known on the possible health effects of (1-3)-β-D-glucan during infancy. The first aim of this research was to compare the specificity of the LAL vs. EIA methods in detecting eight alpha and beta-glucan standards, and their sensitivity for the analysis of (1-3)-β-D-glucan content of common indoor fungal species and indoor dust samples. It was also examined which indoor mold species predict (1-3)-β-D-glucan concentration in field dust samples, and thus whether (1-3)-β-D-glucan can be used as a surrogate for mold exposure. The second aim was to asses the association between (1-3)-β-D-glucan exposure and the prevalence of allergen sensitization and wheezing during the first year of life in a birth cohort of 574 infants born to atopic parents. Common indoor fungal species were cultured from pure ATCC strains on agar media, and analyzed for (1-3)-β-D-glucan content by both the LAL and EIA. (1-3)-β-D-glucan exposure was also measured in settled dust collected from infants’ primary activity rooms using LAL. The primary outcomes at approximately age one included parental reports of recurrent wheezing and allergen sensitization evaluated by skin prick testing to a panel of 15 aeroallergens. This study revealed that most prevalent species in indoor environments, such as Cladosporium and Aspergillus species were the main (1-3)-β-D-glucan contributors followed by Epicoccum nigrum, Wallemia sebi and Penicillium brevicompactum. In contrast, Alternaria alternata did not contribute much to the (1-3)-β-D-glucan load. Exposure to high (1-3)-β-D-glucan concentration was associated with reduced likelihood of both recurrent wheezing and recurrent wheezing combined with allergen sensitization. Similar trends were found between (1-3)-β-D-glucan concentrations and allergen sensitization. Advisors/Committee Members: Reponen, Dr. Tiina.

9. Jian, Zhengwen. Genetic Diversity and Expression Variation in Human Cytochrome P450 Genes.

Degree: PhD, Medicine : Environmental Health, 2008, University of Cincinnati

► Variation in activity of cytochrome P450s is one of the major factors… (more)

▼ Variation in activity of cytochrome P450s is one of the major factors responsible for interindividual difference in drug clearance rate which may cause serious toxicity or inefficacy of clinically used drugs. Such variation was reported to be determined at mRNA level for major P450 genes albeit it to a various degree. Little is known about mechanisms underlying the huge expression variation of most P450 genes among individuals. Identification of genetic variants affecting expression levels of P450 genes can lead to a cost-effective personalized medicine. This dissertation aims to 1) determine the genetic diversity and genetic structure of the CYP1A1_1A2 region; 2) search for determinants of interindividual variation in expression level of seven cytochrome P450 genes; 3) identify cis-acting genetic variants affecting the expression level of CYP1A1 and CYP1A2. Single nucleotide polymorphisms in a 39.6kb segment encompassing the whole CYP1A1 and CYP1A2 genes and the spacer region were identified. The linkage disequilibrium structure, haplotypes and tagSNPs in this region were determined. A humanized BAC-transgenic mouse line was established as a in vivo platform to study activity of different haplotypes of the human CYP1A1_1A2 region. Four factors were identified as major determinants of interindividual variability in expression level of P450 genes in human liver with various contribution for each P450 gene. These four factors include (1) the functional efficacy of global regulators affecting expression level of most active genes; (2) the expression level of specific P450 regulators; (3) exposure to environmental factors responsible for activation or modulation of activity of specific P450 regulators; (4) the presence of cis-acting genetic variants in P450 genes. At least four major cis-acting regulatory SNPs (rSNP) were demonstrated to exist in regulation of CYP1A1 or CYP1A2 expression. One of the four rSNPs was CYP1A1-940C>T (rs4646418), which is located in a G-rich domain about 1kb upstream of the CYP1A1 transcription initiation site, but affects both CYP1A1 and CYP1A2 expression. Another three SNPs – CYP1A1+2573C>T (rs4646422); CYP1A2-2217G>A (rs2069521); CYP1A2+734A>C (rs762551) – were identified to be top candidates as cis-acting genetic variants affecting the expression level of either CYP1A1 (by +2573C>T) or CYP1A2 (by -2217G>A; +734A>C). Advisors/Committee Members: Puga, Alvaro.

Subjects: Biology; Genetics; Toxicology

Keywords: single nucleotide polymorphism (SNP); regulatory SNP (rSNP); linkage disequilibrium (LD); allelic expression imbalance(AEI); CYP1A1; CYP1A2; expression variation

10. Kotowski, Susan E. Understanding a Low Back Pain Pathway: Utilizing MRI and MRS to Link Pain Due to Muscle Inflammation to Changes in Brain Metabolites.

Degree: PhD, Medicine : Environmental Health, 2009, University of Cincinnati

► Low back pain (LBP) has been described as one of the most… (more)

▼ Low back pain (LBP) has been described as one of the most prevalent and significant musculoskeletal problems, with upwards of 85% of the population experiencing LBP at some point in their life. Of those experiencing LBP, up to 85% will not receive a definitive diagnoses as to the cause of the pain. Although a number of known injury sites exist within the low back, because of the ongoing occurrence of LBP, other injury mechanisms must still exist. Complicating pain is the fact that there are several pain pathways as well as there are no objective measures of pain. Recently, it has been shown that exercise induced muscle inflammation, which causes pain, can be analyzed using magnetic resonance imaging (MRI). In addition, magnetic resonance spectroscopy (MRS) has been shown to be able to detect changes in the chemicals in the brain, which are known to respond to painful stimuli. Given these two factors, the goal of this study was to identify whether inflammation in the low back musculature (measured using MRI) could be linked with metabolite changes in the brain known to respond to pain (measured with MRS). Ten healthy subjects (5 males and 5 females) underwent baseline lumbar and brain scans and then completed a lifting and lowering designed to produce inflammation in the erector spinae muscles. Subjects were asked to lift a 9.1 kg carton 8 times per minute until they could no longer do so. Following completion of the lifting task, subjects underwent another lumbar and brain scan. Twenty-four hours later a final lumbar and brain scan series was completed. Subjective ratings of perceived exertion and pain levels were also collected at baseline, immediately following the lifting task, and 24-hours after completing the task. T2 maps were used to analyze muscle inflammation. In an unexpected finding, T2 relaxation times actually decreased significantly following the completion of the lifting task. Glutamate and glutamine, pain markers, were not elevated based on the MRS analysis even though subjective pain ratings were moderate at completion of the task. Twenty-four hours following the lifting task T2 relaxation times were significantly elevated above baseline values, which correlated with subjective pain ratings, which remained elevated. However, no significant changes MRS pain markers were detected. Limitations included a small sample size, limited ability to identify the temporal nature of inflammation and pain, and the use of only healthy subjects. While a definitive link between muscle inflammation and brain response could not be proven, the study did provided some interesting insights for future work. Advisors/Committee Members: Davis, Kermit.

Subjects: Biomedical research; Occupational safety; Public health

Keywords: low back pain; biomechanics; MRI; MRS; muscle inflammation; pain response

11. Liang, Juan. A Nonlinear Mixed Modeling Method to Analyze Allergen Assay Data and the Effects of Exposures Two Indoor Aeroallergens During Infancy on Children at Age Three: The CCAAPS Cohort.

Degree: PhD, Medicine : Environmental Health, 2009, University of Cincinnati

► In chapter II, a nonlinear mixed modeling method is used to analyze… (more)

Subjects: Immunology; Mathematics; Statistics

Keywords: Nonlinear, Immunoassay, Allergen, Allergy

12. LIU, SHENGQIN. EFFECTS OF ARSENIC ON DNA REPAIR AND CELL CELL CHECKPOINTS: INVOLVEMENT IN ARSENIC CO-MUTAGENESIS AND CO-CARCINOGENESIS.

Degree: PhD, Medicine : Environmental Health, 2005, University of Cincinnati

► Arsenic is a well-documented human carcinogen associated with a variety of cancers,… (more)

▼ Arsenic is a well-documented human carcinogen associated with a variety of cancers, though the mechanism of action is unknown. Arsenic is also currently being used to treat some cancers. The paradoxical action of arsenic as both a carcinogen and a chemotherapeutic agent drug may be due to its ability to synergize with other genotoxic agents. Such synergy has been hypothesized to involve effects on DNA repair and/or cell cycle checkpoints. Although arsenic is a carcinogen, attempts to prove arsenic carcinogenesis in animals models have been unsuccessful, leading to the hypothesis that arsenic might act as a co-carcinogen instead of a carcinogen itself. Consistent with a co-carcinogenic model, arsenic by itself does not induce mutations in most bacterial or mammalian systems tested, instead it potentiates the mutagenicity of other agents such as ultraviolet (UV), Benzo(a)Pyrene and N-methyl-N-nitrosourea (NMU). While the mechanism of this co-mutagenicity remains unknown, a possible explanation is that arsenic inhibits DNA repair, specifically nucleotide excision repair (NER). To test this hypothesis, we have completed multiple experiments using low concentrations of arsenite in cultured human cells. Our results showed that at a concentration of 2.5 µM, arsenic induced insertion/deletion mutations in a mutagenesis model using a shuttle vector pZ189, and synergistically enhanced UV mutagenicity in the same model, while it did not alter the UV mutation spectra. In cell culture, arsenic did not increase the generation of UV-induced thymine dimers, but did inhibit the removal of the dimers. In addition, arsenic at 1-5 µM enhanced and prolonged RPA-p34 hyper-phosphorylation induced by UV irradiation, suggesting the persistence of DNA damage. Arsenic did not alter expression of several critical NER proteins or inhibit the incision of UV-induced photoproducts in an in vitro incision assay. Together, these results suggest that arsenic inhibits NER, and perhaps only one subtype of NER, transcription-coupled repair. Further work though is required to identify the mechanism of this inhibition, and the exact process(es) affected. Cell cycle checkpoint pathways are surveillance mechanisms that help maintain genomic integrity. The absence of normal checkpoint functions can lead to premature progression through the cell cycle, insufficient time for DNA repair or failure to eliminate damaged cells. Any of these events will lead to an increased risk of genomic instability and its associated risk of malignant transformation. Current evidence suggested that arsenic may suppress cell cycle checkpoints, leading to genomic instability under insults of DNA- damaging agents. In order to investigate the effects of arsenic on cell cycle checkpoints, we studied the ability of arsenic treatment alone to activate/deactivate checkpoints, as well as arsenic’s ability to modulate checkpoints induced by ultraviolet light (UV) irradiation. Our study showed that sodium arsenite alone at 5 µM did not markedly alter cell cycle progression in HeLa cells, other than initiating an M-phase arrest. In contrast, following UV irradiation arsenite restored the G1 checkpoint and enhanced the S and G2 checkpoints in HeLa cells. These results suggest that arsenic does not inhibit the activation of DNA damage checkpoints after UV, and therefore its function as a co-mutagen or co-genotoxin most likely does not occur via cell cycle checkpoint suppression. Instead, the observed enhancement of cell cycle checkpoints suggests an increase in DNA damage signaling, perhaps due to an inhibition of DNA repair. Advisors/Committee Members: Dixon, Dr. Kathleen.

13. Liu, Xiaolei. Sample Size Calculations in Matched Case-Control Studies and Unmatched Case-Control Studies with Controls Contaminated.

Degree: PhD, Medicine : Environmental Health, 2008, University of Cincinnati

► Matched case-control design is a type of stratification for the control of… (more)

Subjects: Biostatistics

Keywords: bio statatistics; sample size; case control

14. Mack, Elizabeth H. Propofol as a bridge to extubation in the pediatric intensive care unit.

Degree: MS, Medicine : Environmental Health, 2009, University of Cincinnati

► Objective: A significant number of children require long-term sedation and mechanical ventilation,… (more)

Subjects: Health care; Pharmaceuticals; Pharmacology

Keywords: propofol; sedation; pediatric critical care; mechanical ventilation

15. PUTNAM, KAREN T. QUANTIFYING EARLY COGNITIVE DECLINE IN HEALTHY CONTROLS AS RELATED TO THE RISK FACTORS OF APOLIPOPROTEIN E (APOE) e4 AND THE CEREBROSPINAL FLUID (CSF) BIOMARKERS OF b-AMYLOID 1 -42 AND TAU IN ALZHEIMER'S DISEASE.

Degree: MS, Medicine : Environmental Health, 2004, University of Cincinnati

► Objectives: The elderly account for an increasingly significant proportion of the overall… (more)

▼ Objectives: The elderly account for an increasingly significant proportion of the overall population in the United States. Incidence rates of Alzheimer’s disease double with each five years of age reaching an estimated prevalence of 45% by age 85 years. The objectives of this study were to compare neuropsychological composites scores in asymptomatic controls stratified by known biologic risk factors for AD to explore early signals of cognitive decline. Methods:Participants were enrolled in the National Institute of Mental Health (NIMH) longitudinal protocol of Biomarkers in Older Controls “At Risk” for Dementia (BIOCARD). Neuropsychological composite index scores were examined for early signals of decline in a baseline cross-sectional sample of 199 healthy control subjects stratified by the known AD risk factors of APOE ε4 and advanced aging. Additionally, neuropsychological indices were correlated with the CSF proteins of β-amyloid 1-42 and tau in 57% of these subjects. Results: Cognitive z scores indices of word memory learning and story memory learning were influenced by the presence of the APOE ε4 allele. These memory indices, along with visuospatial abilities were also influenced by advanced aging. The cognitive index domains of semantic language and visuospatial attention did not appear sensitive to early signals of decline in this sample. CSF tau levels were highly correlated with age. Composite indices of word memory learning and visuospatial abilities were also associated with CSF tau levels. CSF β-amyloid 1-42 was correlated with age, but not associated with any of the cognitive indices. Conclusions: Memory is typically the first cognitive domain to show signs of impairment in AD. The memory composite measures reported here were sensitive to both the presence of the APOE ε4 allele and one of the known AD CSF biomarkers in healthy, cognitively asymptomatic controls. Careful longitudinal follow-up will be necessary to assess the sensitivity and specificity of these measures as clinical tools in quantifying the early stages of MCI. Advisors/Committee Members: Dietrich, Dr. Kim N.

Subjects: Health Sciences, Mental Health

Keywords: early cognitive decline in asymptomatic controls, z scores, β-amyloid 1-42 , tau, Alzheimer's disease

16. Seo, Sung-Chul. Development and Application of a New Methodology for Separation and Analysis of Submicrometer-Sized Fungal Particles in Laboratory and Field Study.

Degree: PhD, Medicine : Environmental Health, 2007, University of Cincinnati

► Mold exposure is associated with adverse health effects, but spore counts have… (more)

▼ Mold exposure is associated with adverse health effects, but spore counts have not shown strong correlation with health outcomes. Submicrometer-sized fungal fragments have been suggested as potential contributors to the adverse health effects because of their small size, large quantities, and biological properties. However, the contribution of submicrometer-sized fungal fragments to mold exposure and adverse health effects is poorly characterized due to the lack of suitable sampling and analytical methods. The purposes of this research were to test and optimize a newly developed Fragment Sampling System combined with (1→3)-β-D-glucan assay for separation and analysis of submicrometer-sized fungal fragments, to apply the new methodology to characterize size-fractionated particulate (1→3)-β-D-glucans aerosolized from fungi grown on MEA, ceiling tile, and gypsum board for one and six months, and to field-test the new methodology in moldy homes. Penetration and spore bounce tests were performed for optimization using PSL particles, Aspergillus versicolor, and Stachybotrys chartarum. (1→3)-β-D-glucan of collected samples was analyzed by the Limulus Amebocyte Lysate assay. This investigation confirmed the successful separation of submicrometer-sized fungal fragments from intact spores and the feasibility of quantification of these samples. The results also revealed that aerosolization of particulate (1→3)-β-D-glucan can be influenced by the material type and fungal species. The release of particles and particulate (1→3)-β-D-glucan increased with the age of the fungal culture. A poor correlation between numbers of submicrometer-sized particles and (1→3)-β-D-glucan mass was observed. The field study showed that the actual contribution of submicrometer-sized fungal fragments to total mold exposure was higher than that estimated by laboratory-generated data. Moreover, the amount of spore-sized (1→3)-β-D-glucan did not correlate with the amount of fragment-sized (1→3)-β-D-glucan. In conclusion, this research indicates that the new methodology is a promising tool for separation and analysis of submicrometer-sized fugal fragments. A considerable amount of submicrometer-sized particulate (1→3)-β-D-glucan was observed in the field study. However, numbers of submicrometer-sized particles or the amount of spore-sized (1→3)-β-D-glucan cannot be used to estimate the (1→3)-β-D-glucan mass of fungal fragments due to a poor correlation between these parameters. Therefore, measurement of fungal fragments should be included when assessing mold exposure in moldy indoor environments. Advisors/Committee Members: Reponen, Dr. Tiina.

Subjects: Health Sciences, Public Health

Keywords: Beta-glucan; fragment; mold; building material; aerosolization

17. Standridge, Jeremy Shawn. Postural instability and chronic low level manganese exposure: A cross-sectional pilot study of residents in Marietta, Ohio.

Degree: MS, Medicine : Environmental Health, 2008, University of Cincinnati

► Objective: To evaluate postural balance and biological markers of a population chronically… (more)

Subjects: Environmental science; Public health

Keywords: manganese; hair; blood; balance; sway; Marietta

18. VENDITTO, CARMEN. TRANSCRIPTIONAL SIGNATURES DURING THE DEVELOPMENT OF METAL-INDUCED ACUTE LUNG INJURY: ROLE OF SURFACTANT PROTEIN B.

Degree: MS, Medicine : Environmental Health, 2006, University of Cincinnati

► Acute lung injury is the rapid onset of lung dysfunction with many… (more)

Keywords: Acute lung injury; Surfactant protein B; Metallothionein

19. Wilson, Amy C. High Prevalence of the Metabolic Syndrome and Associated Left Ventricular Hypertrophy in Pediatric Renal Transplant Recipients.

Degree: MS, Medicine : Environmental Health, 2008, University of Cincinnati

► Background: Individual cardiovascular (CV) risks are common after pediatric renal transplant. The… (more)

Subjects: Health care

Keywords: pediatric; renal transplant; metabolic syndrome; left ventricular hypertrophy

20. WURZELBACHER, STEVEN JOSEPH. CRITERIA FOR EVALUATING AN OCCUPATIONAL SAFETY AND HEALTH PROGRAM.

Degree: PhD, Medicine : Environmental Health, 2006, University of Cincinnati

► Introduction: Many employers and regulators today rely primarily on a few past… (more)

▼ Introduction: Many employers and regulators today rely primarily on a few past injury/ illness metrics as criteria for rating the effectiveness of occupational safety and health (OSH) programs. Although such objective ratings are necessary to assess program success, they are not sufficient for developing proactive safety and ergonomic plans. Methods: The goals of this research were to create objective (past loss data) and subjective (company self-assessment ratings of exposure and control) benchmarks that could be readily used by companies to monitor the effectiveness of their OSH programs. The main hypothesis was that these new benchmarks would be predictive of three standard future loss outcomes. Subjective Benchmarks: Surveys were sent to 197 companies in early 2003 and 33 completed questionnaires were used for final analysis. Individual question responses were regrouped into 12 index scores to capture assessments of company exposure and control. Objective Benchmarks: Workers compensation data sets from 1/1/99 to 12/31/03 were downloaded 10/4/04 for the 33 companies and a series of 10 past loss metrics were developed. Results: The following variables were found to be significant predictors as hypothesized in stepwise multiple regression models: WC Case Rate 2003 outcome: Subjective: Hazard Prevention and Control, Safety (p = 0.01), Hazard Prevention and Control, General (p < 0.001). Objective: Musculoskeletal Indemnity Case Rate, 1999-2001 (p < 0.01). Indemnity Case Rate 2003 outcome: Subjective: Hazard Identification and Assessment (p = 0.01), and All Prevention Program Elements (p = 0.01). Objective: Musculoskeletal Indemnity Case Rate, 1999-2001 (p < 0.01) and Reporting Delay Average Days, 1999-2001 (p = 0.01). State Weighted WC Cost per 1 FTE per Year (2003) LN Transformed outcome: Subjective: None. Objective: None. Summary and Conclusions: The similar strengths of Subjective and Objective variables in predicting future losses indicate that both the regular tracking of past loss outcomes and the subjective auditing of loss prevention and reduction efforts within a company are useful processes. Both types of benchmarks are required to fully develop data-driven, safety and ergonomic plans that are reactive to past exposures and proactive in identifying system deficiencies that drive future losses. Advisors/Committee Members: Bhattacharya, Dr. Amit.

Keywords: occupational safety and health programs; questionnaire; survey; ergonomics; criteria; benchmarks; subjective; loss data

21. ZHANG, GE. STATISTICAL METHODS IN GENETIC ASSOCIATION.

Degree: PhD, Medicine : Environmental Health, 2007, University of Cincinnati

► Association studies offer great promise in dissecting the genetic basic of human… (more)

▼ Association studies offer great promise in dissecting the genetic basic of human complex diseases. The rapid expansion of genomic information and the cost-effective genotyping technologies have enabled us to systematically interrogate the role of human genetic variation in common diseases by genome-wide association (GWA) mapping. However, the scale and complexity of such studies will raise significant challenges in study design and data analysis. In this dissertation, we investigated several statistical problems that relevant to population-based association studies and the fine-scale mapping of genetic variants that influence susceptibility to complex diseases. First, we developed a variance-based effect size estimator for the locus-specific genetic effect. Comparing to the traditional measures, the proposed estimator is less sensitive to the risk allele frequency and the population prevalence of the disease. We demonstrated the sample size requirement would be considerable large to obtain an accurate estimate on moderate genetic effect and the sample size will increase exponentially with increased demand for precision. We next compared the power of different association test statistics. We observed that the genotype based single-locus tests is generally more powerful than the multi-locus or haplotype based statistics, especially for risk alleles far from additive; and the power of genotype based tests can be uniformly improved by applying the ordered restriction on genotypic risks. Finally, we tested different GWA strategies and explored the factors that may influence the power of GWA studies by extensive simulations using empirical genotype data from the HapMap ENCODE Project. Our results indicate that current commercial genome-wide typing products are capable of capturing most of the common risk variants; however, their power in detecting rare risk variants or variants within recombination hot spots is not satisfactory. We also showed that the properties of the risk variants (e.g. allele frequency, local recombination rate, and functional category) have significant impacts on the power of GWA. The results generated from this comprehensive exercise would be helpful for developing efficient GWA studies. Advisors/Committee Members: Chakraborty, Ranajit.

Subjects: Biology, Genetics

Keywords: Linkage disequilibrium; Haplotype; Genetic association; Genome-wide association; Association test